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Effect of Vitis vinifera hydroalcoholic extract against oxaliplatin neurotoxicity: in vitro and in vivo evidence.

ABSTRACT: Oxaliplatin treatment is associated with the development of a dose-limiting painful neuropathy impairing patient's quality of life. Since oxidative unbalance is a relevant mechanism of oxaliplatin neurotoxicity, we assessed the potential antioxidant properties of Vitis vinifera extract in reducing oxaliplatin-induced neuropathy as a valuable therapeutic opportunity. A hydroalcoholic extract of Vitis vinifera red leaf was characterized and tested in primary rat astrocyte cells treated with oxaliplatin (100??M). Oxaliplatin lethality in the human adenocarcinoma cell line HT-29 was evaluated in the absence and presence of the extract. In vivo, pain hypersensitivity was measured in a rat model of neuropathy induced by oxaliplatin and ex vivo molecular targets of redox balance were studied. Vitis vinifera extract (50??g mL^-1, 4?h incubation) significantly reduced the oxaliplatin-dependent superoxide anion increase and lipid peroxidation in rat astrocytes but did not interfere with the mortality elicited by oxaliplatin in HT-29 cancer cells. In oxaliplatin-treated rats, a repeated daily administration of the Vitis vinifera extract (300?mg?kg^-1, p.o.) significantly prevented mechanical and thermal hypersensitivity to noxious and non noxious stimuli. mRNA and protein levels of Nrf2 were normalized in spinal cord and DRGs. Moreover, in the spinal cord, the extract significantly decreased the activation of astrocytes. Vitis vinifera reduced oxidative damages and relieved pain without influencing oxaliplatin anti-cancer activity.

SUBMITTER: Micheli L

PROVIDER: S-EPMC6156221 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Effect of Vitis vinifera hydroalcoholic extract against oxaliplatin neurotoxicity: in vitro and in vivo evidence.

Micheli Laura L Mattoli Luisa L Maidecchi Anna A Pacini Alessandra A Ghelardini Carla C Di Cesare Mannelli Lorenzo L

Scientific reports 20180925 1

Oxaliplatin treatment is associated with the development of a dose-limiting painful neuropathy impairing patient's quality of life. Since oxidative unbalance is a relevant mechanism of oxaliplatin neurotoxicity, we assessed the potential antioxidant properties of Vitis vinifera extract in reducing oxaliplatin-induced neuropathy as a valuable therapeutic opportunity. A hydroalcoholic extract of Vitis vinifera red leaf was characterized and tested in primary rat astrocyte cells treated with oxalip ...[more]

PMID: 30254294

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Project description:Except for specific vaccines and monoclonal antibodies, effective prophylactic or post-exposure therapeutic treatments are currently limited for COVID-19. Propolis, a honeybee's product, has been suggested as a potential candidate for treatment of COVID-19 for its immunomodulatory properties and for its powerful activity against various types of viruses, including common coronaviruses. However, direct evidence regarding the antiviral activities of this product still remains poorly documented. VERO E6 and CALU3 cell lines were infected with SARS-CoV-2 and cultured in the presence of 12.5 or 25 μg/ml of a standardized Hydroalcoholic Extract acronym (sHEP) of Eurasian poplar type propolis and analyzed for viral RNA transcription, for cell damage by optical and electron microscopy, and for virus infectivity by viral titration at 2, 24, 48, and 72 h post-infection. The three main components of sHEP, caffeic acid phenethyl ester, galangin, and pinocembrin, were tested for the antiviral power, either alone or in combination. On both cell lines, sHEP showed significant effects mainly on CALU3 up to 48 h, i.e., some protection from cytopathic effects and consistent reduction of infected cell number, fewer viral particles inside cellular vesicles, reduction of viral titration in supernatants, dramatic drop of N gene negative sense RNA synthesis, and lower concentration of E gene RNA in cell extracts. Interestingly, pre-treatment of cells with sHEP before virus inoculation induced these same effects described previously and was not able to block virus entry. When used in combination, the three main constituents of sHEP showed antiviral activity at the same levels of sHEP. sHEP has a remarkable ability to hinder the replication of SARS-CoV-2, to limit new cycles of infection, and to protect host cells against the cytopathic effect, albeit with rather variable results. However, sHEP do not block the virus entry into the cells. The antiviral activity observed with the three main components of sHEP used in combination highlights that the mechanism underlying the antiviral activity of sHEP is probably the result of a synergistic effect. These data add further emphasis on the possible therapeutic role of this special honeybee's product as an adjuvant to official treatments of COVID-19 patients for its direct antiviral activity.

Project description:Background: Punica granatum extracts have been prescribed in traditional medicine for management of a variety of disease conditions including microbial infections. Generation of scientific evidence for validation of P. granatum peel extract's anti-pathogenic efficacy is required. Methods: Hydroalcoholic extract of P. granatum peel (PGPE), prepared by microwave assisted extraction method was evaluated for its quorum-modulatory potential against two different human-pathogenic bacteria viz. Chromobacterium violaceum and Pseudomonas aeruginosa. Results: This extract was able to modulate in vitro production of quorum sensing-regulated pigments in both these test bacteria at ≥5 μg/ml. Virulence traits of P. aeruginosa like haemolytic activity, and biofilm formation were negatively affected by the test extract, and it also made P. aeruginosa more susceptible to lysis by human serum. Antibiotic susceptibility of both test bacteria was modulated owing to pre-treatment with PGPE. Exposure of these test pathogens to PGPE (≥0.5 μg/ml) effectively reduced their virulence towards the nematode Caenorhabditis elegans. Repeated subculturing of P. aeruginosa on PGPE-supplemented growth medium did not induce resistance to PGPE in this notorious pathogen, and this extract was also found to exert a post-extract effect on P. aeruginosa. Individual constituent phytocompounds of PGPE were found to be less efficacious than the whole extract. PGPE seemed to interfere with the signal-response machinery of P. aeruginosa and C. violaceum. PGPE also exhibited notable prebiotic potential by promoting growth of probiotic strains- Bifidobacterium bifidum and Lactobacillus plantarum at ≤50 μg/ml. Conclusions: This study indicates PGPE to be an effective antipathogenic and prebiotic preparation, and validates its therapeutic use mentioned in traditional medicine. This study also emphasizes the need for testing any bioactive extract at broadest possible concentration range, particularly in vivo, so that an accurate picture of dose-response relationship can emerge.

Dataset Information

Effect of Vitis vinifera hydroalcoholic extract against oxaliplatin neurotoxicity: in vitro and in vivo evidence.

Publications

Effect of Vitis vinifera hydroalcoholic extract against oxaliplatin neurotoxicity: in vitro and in vivo evidence.

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